Tocilizumab degradation via photo-catalytic ozonation process from aqueous

Following the advent of the coronavirus pandemic, tocilizumab has emerged as a potentially efficacious therapeutic intervention. The utilization of O3-Heterogeneous photocatalytic process (O3-HPCP) as a hybrid advanced oxidation technique has been employed for the degradation of pollutants. The present study employed a solvothermal technique for the synthesis of the BiOI-MOF composite. The utilization of FTIR, FESEM, EDAX, XRD, UV–vis, BET, TEM, and XPS analysis was employed to confirm the exceptional quality of the catalyst. the study employed an experimental design, subsequently followed by the analysis of collected data in order to forecast the most favorable conditions. The purpose of this study was to investigate the impact of several factors, including reaction time (30–60 min), catalyst dose (0.25–0.5 mg/L), pH levels (4–8), ozone concentration (20–40 mMol/L), and tocilizumab concentration (10–20 mg/L), on the performance of O3-HPCP. The best model was discovered by evaluating the F-value and P-value coefficients, which were found to be 0.0001 and 347.93, respectively. In the given experimental conditions, which include a catalyst dose of 0.46 mg/L, a reaction time of 59 min, a pH of 7.0, and an ozone concentration of 32 mMol/L, the removal efficiencies were found to be 92% for tocilizumab, 79.8% for COD, and 59% for TOC. The obtained R2 value of 0.98 suggests a strong correlation between the observed data and the predicted values, indicating that the reaction rate followed first-order kinetics. The coefficient of synergy for the degradation of tocilizumab was shown to be 1.22. The catalyst exhibited satisfactory outcomes, but with a marginal reduction in efficacy of approximately 3%. The sulfate ion (SO42−) exhibited no influence on process efficiency, whereas the nitrate ion (NO3−) exerted the most significant impact among the anions. The progress of the process was impeded by organic scavengers, with methanol exhibiting the most pronounced influence and sodium azide exerting the least significant impact. The efficacy of pure BiOI and NH2-MIL125 (Ti) was diminished when employed in their pure form state. The energy consumption per unit of degradation, denoted as EEO, was determined to be 161.8 KWh/m3-order.

their original or modified form at different concentrations 4 .Therefore, medicinal compounds specific to the treatment of corona virus during the pandemic condition was predictable.The primary sources of pharmaceutical chemicals in the environment include home usage, pharmaceutical industry and hospital waste, and unintentional drug releases 5 .The presence of medicinal compounds in their parents and metabolized form causes potential risks that have been mentioned in previous studies.Medicinal compounds are in the group of compounds resistant to decomposition and, because of their complex structure, they face a challenge in common treatment processes 6 .The specific advantages and disadvantages can vary depending on the type of treatment method employed and the characteristics of the wastewater being treated.The selection of the most appropriate treatment method should consider factors such as the scale of operation, regulatory requirements, and the specific contaminants present in the wastewater 7 .Organic pollutants, can be rapidly oxidized and completely degraded using chemical methods 8 .The best way to treat organic wastewater is to use advanced oxidation processes (AOPs).AOPs are advantageous because of their high mineralization efficiency, simple operation, small footprint, high rate in oxidation, and lack of final hazardous pollution.Various AOPs can degrade organic pollutants by generating highly active radicals, including photocatalytic reactions, Fenton, sonochemical oxidation, electrochemical oxidation reactions, and catalytic ozonation 7 .Organic pollutants are oxidized and mineralized by AOPs, which produce reactive oxygen species (ROS s ) such as hydroxyl radicals (OH • ), superoxide radicals (O 2 •− ), sulfates (SO 4 •− ) and non-radicals like H 2 O 2 and 1 O 2 that have oxidation and reduction potential (ORP) above 2 eV [9][10][11] .Due to its stability, low toxicity, affordability, and potent oxidative capabilities, heterogeneous photocatalysis of semiconductors have become one of the most important, environmentally sound, and widely applicable technologies 12 .This is because the photocatalyst completely mineralizes the pollutant without producing any hazardous byproducts 13 .In actuality, oxidation-reduction processes are used in heterogeneous photocatalysis to convert photons that are absorbed by semiconductors into chemical energy.Through the generation of highly oxidizing free radicals, excited catalysts are able to directly degrade contaminants that are adsorbed on their surfaces 14 .A study of the heterogeneous photocatalysis process (HPCP) focused on introducing new semiconductor materials as a photocatalyst.Several semiconductors, including MOFs, g-C 3 N 4 , and metal family oxides with slim band gaps, were used to extend the response spectrum to the visible spectrum 15 .UV-C activation is used to activate classic semiconductors like TiO 2 , CdO, CdSe, and ZnO.Solar radiation can't be used as a source of energy for these classic semiconductors due to their wide band gaps.It is activated by ultraviolet radiation, which represents less than 4% of solar radiation, and for these reasons, their use is limited 16 .Increasingly, metal-organic frameworks (MOFs) have been attracting attention for their ability to remove pollutants via photocatalysis and adsorption mechanism.Recent environmental studies have investigated various MOF-based photocatalysts.NH 2 -MIL125 (Ti) is a Ti-based amino-functioned MOF chosen for its non-toxicity, photo/water stability, and visible-light absorption 17 .As a result, MOFs can be restricted from being used as independent photocatalysts due to low migration efficiency, low charge separation, and poor conductivity.Several approaches have been suggested with the aim of enhancing the photocatalytic characteristics of MOFs.One of these methods is heterojunction structures 18 .Semiconductors based on bismuth are regarded as eco-friendly, stable, and nonpoisonous photocatalysts with high visible light absorbency.BiOI is a superior photocatalyst due to its layered structure, unique electrical characteristics, and suitable band gap (BG = 1.62-1.93eV).In spite of this, BiOI has limited application due to much carrier recombination.In heterojunctions, charge separation and hole recombination can be reduced, thus overcoming this disadvantage 19 .NH 2 -MIL125 (Ti) serves as an excellent support material for BiOI due to its favorable properties, including high surface area and porosity.These characteristics facilitate the effective adsorption of BiOI nanoparticles, thereby promoting interfacial contact between BiOI and NH 2 -MIL125 (Ti) and enhancing charge transfer and separation efficiency.Notably, NH 2 -MIL125 (Ti) exhibits exceptional electron transfer properties attributed to its intrinsic electronic structure and the presence of amino functional groups.This enables efficient electron transfer from BiOI to NH 2 -MIL125 (Ti), effectively reducing charge recombination and further enhancing charge separation efficiency 20 .Moreover, the combination of BiOI and NH 2 -MIL125 (Ti) displays synergistic effects, resulting in improved photocatalytic performance and enhanced charge separation efficiency.The proper alignment of energy levels between BiOI and NH 2 -MIL125 (Ti) is crucial for facilitating efficient charge separation.Furthermore, NH 2 -MIL125 (Ti)'s stability and durability make it an ideal support material for BiOI, ensuring structural integrity and preventing the aggregation or degradation of BiOI nanoparticles.Consequently, this characteristic guarantees sustained photocatalytic performance and high charge separation efficiency over extended operational periods 21 .Numerous endeavors have been undertaken to hinder the deactivation of photocatalysis and enhance the performance of HPCP.The ozone enhanced photocatalytic oxidation process has garnered significant scrutiny due to its resilient capability in enhancing the efficacy of HPCP when eliminating organic compounds, commonly referred to as O 3 -HPCP 22 .Ozone is essential to the breakdown of organic matter because, in comparison to other processes, it is more affordable, ecologically benign, easily obtainable, and has a simple operating technique 23 .In this study, it was found that O 3 -HPCP increases reactive oxygen species, leading to faster mineralization rates of resistant organic compounds.O 3 -HPCP uses free radicals with higher ORP s than ozone.Tocilizumab, the target pollutant, is broken down in O 3 -HPCP near the catalyst surface and reaction media 24 .Previous studies such as Liu and coworkers 25 and Zhu and coworkers 26 show the use of O 3 -HPCP has been used in the last few years to remove resistant organic compounds.Given the global prevalence of the coronavirus pandemic in recent years, and its continued presence in some countries necessitating the use of medications containing tocilizumab compounds, it is imperative to offer effective processes for treating wastewater containing these compounds.This study represents the inaugural investigation into the efficacy of O 3 -HPCP for the purpose of assessing its ability to removal the tocilizumab.Based on the explanations provided, the objectives of this research are divided into three parts.
(1): Synthesis and characterization of BiOI-NH 2 -MIL125(Ti) (in abbravation BiOI-MOF) as a novel Co-MOF, (2): Optimization of parameters of O 3 -HPCP for the degradation of tocilizumab which was found in different concentrations during the corona outbreak in water environments such as hospital and pharmaceutical

Materials and reagents
All chemical was purchased from trustworthy suppliers.The analytical grade samples did not require any further purification.Potassium iodide [KI], bismuth nitrate pentahydrate [Bi(NO 3 )

Construction of NH 2 -MIL125(Ti)
As reported in previous literature, the solvothermal technique was used to create NH 2 -MIL-125 (Ti) with some adjustments to the amount of substances 27,28 .A solution consisting of 33 mL N, N-dimethylformamide (DMF), 4 mL of methanol, 1.55 g of 2-aminoterephthalic acid, and 2.2 mL of tetrabutyl titanate was mixed for 40 min at room temperature in an ultrasonic bathroom.Using a Teflon-lined autoclave allowed the mixture solution to be maintained at 180 °C for 60 h.The procedure was completed with the filtration of the suspension, followed by multiple rinsing with methanol and DMF, and finally drying in an electric furnace at 75 °C.

Construction of BiOI-NH 2 -MIL125(Ti)
The literature was used to create BiOI-MOF, with a few modifications in the quantity of materials 27 .Ultrasonic waves were used to dissolve 2 g of MOF in 40 cc deionized water with KI (1.2 mmol) for 30 min.The solution was combined with 13 mL of ethylene glycol and then delicately diluted with Bi(NO 3 ) 3 .5H 2 O.The suspension was stirred intensively in a water bath of approximately 80°C for a duration of 30 min.The catalyst was sifted during refinement, washed using ethanol three times, and rinsed with distilled water, and then heated to 80°C.

Construction of BiOI
A comparative analysis was conducted to examine the physical, chemical, and other distinguishing features of BiOI, MOF and BiOI-MOF.Pure BiOI was synthesized without the presence of MOF in the solution.

Characterization
An FT-IR spectrophotometer (Sipotlight 220i FT-IR Microscopy Systems) was used to analyze the molecular composition of MOF, BiOI, and BiOI-MOF.The Rigaku/ZSX Primus 500 XRD diffractometer was used to conduct X-ray diffraction analysis.Average sample sizes were calculated using Scherrer's equation (Eq. 1) 29 .
Here, the crystal sample size is represented by D, λ symbolizes the angle of diffraction, K represents a dimensionless constant, β represents the FWHM (full with half maximum) of the diffraction peak, and θ refers to the angle of diffraction.
The UV-visible spectrum (UV-Vis DRS) was analyzed to investigate the optical properties and structural characteristics using the Agilent Cary 60 spectrophotometer.Band gap energy was determined with the assistance of the Tauc equations (Eqs.2,3) 30 .
where α is coefficient of absorption, v is light frequency, A is a constant parameter, hʋ is the photon energy of the incident photons, h is Planck's constant, and Eg is the band-gap of sample.To determine the band-gap energy of BiOI, a direct band-gap semiconductor, (Eq.2) was applied.Similarly, for MOF, an indirect band-gap semiconductor, (Eq. 3) was utilized.The samples' morphology was surveyed using a FE-SEM (UN41219SEM) operating at a vacuum of ≥ 1.2 × 10-4 mbar.The utilization of energy dispersive spectroscopy (EDS) was employed in order to examine the elemental mapping as well as the integrity of the samples.The acquisition of a transmission electron microscopy image (TEM) was achieved by applying a stimulating voltage of 100 kV using the Shimadzu JEM-1200 EX.The nitrogen adsorption at 77 K allowed for the determination of the volume, pore size, and surface area distribution of BiOI-MOF.The samples underwent a process of degassing in their original position for a duration of 12 h at a temperature of 200°C, while a vacuum was present.The technique utilized for the determination of surface areas in the context of the linear correlation between p/p0 and surface areas was the Brunauer-Emmet-Teller (BET) technique.Analysis of the XPS characterizations was conducted with an ESCALAB250XI electron spectrometer.

Installing O 3 -HPCP
A cylindrical unit measuring 600 mL, characterized by a diameter of 10 cm and a height of 20 cm, was employed for the O3-HPCP experiments.A quartz sheath (4.5 × 16 cm) was positioned centrally in a horizontal orientation (Fig. 1).The experiments were conducted utilizing a batch system under the conditions of an ambient temperature (25 ± 2 °C).A solution of tocilizumab, (0.1 g), was thoroughly dissolved in deionized water to create a stock solution with a concentration of 100 mg/L.The reactor was equipped with the PHILIPS TUV-PLL6W model, featuring Low-pressure, a maximum wavelength ranges of 385 nm and 6 W. A micro-diffuser was employed to introduce a consistent flow of ozone gas into the reaction medium by pumping gas that is high in oxygen through an ozone device (Oneteck, Iran).Regulating the O 3 concentration by adjusting the flow rate of feed oxygen.The magnetic mixing was employed to homogenize the solution within the reactor.For the measurement of tocilizumab, 10 ml of the reaction mixture was taken from the reactor, passed through 0.22 m syringe filters, and finally injected into high-performance liquid chromatography (HPLC).The mean values were calculated by taking the average of the results from the three trials for each test, and the tocilizumab, TOC, and COD reduction rates in the O 3 -HPCP process were determined using (Eq.4) 29 .
The quantity of tocilizumab, COD, and TOC (mg/L) that is present initially and after a certain point in time is denoted by C o and C t , respectively.

The variables optimization of O 3 -HPCP based on CCD
The CCD approach within response surface methodology was employed in order to optimize the O3-HPCP for the tocilizumab degradation.Table 1 presents an overview of the various variables within a specified range.
The design of the CCD served as the foundation for the fifty trials documented in Table S.1, with the intention of tocilizumab degradation.The representation of the tocilizumab degradation through O 3 -HPCP can be expressed through the utilization of a mathematical model known as a second-order polynomial model (Eq.5) 31 : Tocilizumab removal (%) is represented by Y., the intercept is β 0 , the linear, quadratic, and interaction effect coefficients of the variables are β i , β ii , and β ij , respectively, the coded testing classes of the variables are xi and x j , the number of independent variables is k, and the residual error is e.To allow comparisons between components with differing units, an encoding of each variable's value was calculated using (Eq.6).
where the coded value of the variable is X i , ∆ x which is the difference between the high and low values of the variable, X 0 represents the low value of the variable.Analysis of variance (ANOVA) was used to find the interaction between response and variables using P-values and F-values.The correlation coefficients are R 2 and R 2 adj .Also, R 2 predicts were applied.
Under ideal circumstances, an analysis was carried out on the effects of different light sources (visible light, UV-A, and UV-C), the rate of the kinetic reaction, the impact of synergistic effect, variations in wavelength scanning, and energy consumption.

Analytical methods
After each trial, a sample was gathered and filtered with a 0.45 µ micropure-filter and subsequently injected into the HPLC.A HPLC system with a fluorescence detector was utilized to measure the tocilizumab concentration.Utilization of the FF-C18 non-porous column, which was packed with 2 μm particles (50 mm × 3.2 mm inner diameter, Kyoto, Japan) was performed.The mobile phase A was formulated with 0.1% trifluoroacetic acid (TFA), while solvent B was composed of 30% isopropanol, 70% acetonitrile, and 0.1%.Following a linear elution of A/B (90:10) to A/B (70:30) for one min, a linear elution of A/B (70:30) to A/B (55:45) for six min, a linear elution of A/B (55:45) to A/B (5:95) for two min, a linear elution of A/B (95:5) to A/B (0:100) for one min, and a final isocratic elution of A/B (90:10) for one min was utilized to create the gradient profile.0.5 mL/min was established as the rate of flow for the mobile phase, while the column temperature was fixed at 75 °C32 .The TOC analysis was conducted using Analytikjena's Multi C/N 3100 TOC Analyzer.As outlined in the conventional approach, COD levels were measured through titrimetric analysis (5220-C; closed-reflux) 33 .

Reaction kinetics and synergic effect
The decay of tocilizumab in the ideal circumstances of the O 3 -HPCP procedure was demonstrated to follow a first-order reaction (Eq.7) 34 .
In the context, C t represents the residual concentration, C 0 represents the initial concentration of tocilizumab (mg/L).The variable t denotes the reaction time (min), and k app denotes the rate constant (1/min).
An evaluation of the synergistic effect was conducted under ideal conditions of parameters determined by (Eq.8) 35 .

Reusability of catalyst, quenching test and anions effect
Six experiments were conducted to assess the reusability of catalyst and durability of the process under the best O 3 -HPCP conditions.The reaction of free radicals with organic radical scavengers and the effect of anions were investigated under ideal conditions.

Electrical energy demand
The electricity energy operating (EEO) of the O 3 -HPCP under ideal conditions as determined by (Eq.9) 36 .
The power consumption, P (kWh), and the volume of treated solution, V (L), can be found.

Ethical statement
The above study has been approved by the Ethics Committee of the Baqiyatallah University of Medical Sciences (Code: IR.BMSU.BLC.1402.025). (5)

Results and discussion
Characters of catalyst XRD Figure 2 represent the X-ray diffraction patterns of BiOI, NH 2 -MIL125, and BiOI-MOF samples.BiOI with four major peaks illustrated in (Fig. 2a).These peaks numbered (102), ( 110), (200), and (212).All diffraction peaks from synthesized BiOI (JCPDS no.10-0445) indicated a tetragonal phase.There indicates high crystallinity through the sharp and distinct peaks.Our previous study, shows the similar results 24 .In (Fig. 2b) presented XRD patterns of MOF.The standard pattern revealed MOF peaks at 6.8°, 9.7°, 11.8°, 15.7°, 16.5°, 17.8°, 19.1°, and 19.5°.Analysis of XRD patterns indicates that the orthorhombic phase has a correlation to lattice parameters of a = 14.89Å, b = 5.9 Å, and c = 18.95 Å.By utilizing BDC and NH 2 BDC as a connecting agent, it becomes possible to generate three-dimensional pores within a sequence of corner-sharing TiO 6 .A comparable findings was reported by Mehralipour and their associates 37 .Finally, the BiOI-MOF nanocomposite structure exhibits certain peaks, similar to the ones observed in the pure BiOI and MOF, as demonstrated in (Fig. 2c).There is a significant change in the positions and strength of the peaks.The XRD results aligned with those of Du and co-workers' study 38 .Using Scherrer's equation (Eq.1), the dimensions of the crystalline structures in the BiOI, MOF, and BiOI-MOF specimens were ascertained to measure 26/5, 47/8, and 37/1 nm, correspondingly.

FT-IR
FTIR spectroscopy was utilized to examine the organic moieties of the samples (Fig. 3).
The main peaks appeared at 570.1, 1311.8,1383.5, 1628.1, and 3532.4 cm −1 in pure BiOI.The vibrational frequency of the A 2 u type Bi-O bond is symmetrical at 570.1 cm −1 .The BiOI demonstrates a powerful adsorption between 1300-1700 cm −1 , along with a prominent peak in the range of 3185 cm −1 to 3478 cm −1 that is caused by the flexural (-OH) and tensile vibrations (-OH) of isolated water molecules on the BiOI's surface.Results that matched those reported by Vahabirad and his team 39 .The interval from 500 to 1500 cm −1 observed in MOF displayed distinctive attributes commonly associated with organic compounds, as illustrated in (Fig. 3b).The 1255 cm − 1 and 1622 cm −1 peaks can be utilized to ascertain the typical tensile strength of aromatic N-H flexural vibrations and C-N amines, correspondingly.The obtained results indicate the presence of two distinct peaks at 1535 cm −1 and 1433 cm −1 , thereby providing evidence for the existence of the carboxylate bond.Additionally, the absorption peaks that appear at 450 cm −1 are linked to the customary vibrations of Ti-O-Ti bonds.Both symmetric and asymmetric tensile vibrations of primary amines were observed to exhibit extensive peaks at approximately 4000 cm −1 .Zhao and colleagues reported significant peaks at 773, 1258, 1385, 1539, 1662, 2524, 3059, 3348, and 3450 cm −140 .A depiction of the FT-IR spectrum of the BiOI-MOF can be observed in (Fig. 3  c).The highest peaks of the spectrum were identified at 565.5, 807, 1313, 1382, 1624, and 3464 cm −1 .Amine groups, alkyl halides, -CH 3 signals, N-O nitro compounds, C-H stretching, and C-H bands can be identified at the peaks.Studies conducted by Han and Du and their teams of researchers verified the heterojunction between BiOI at NH 2 with NH 2 -MIL125(Ti) 27,38 .

Morphology analysis
The FESEM, EDX, and EDS mapping technique applied to analyze the samples (Fig. 4).The morphology of thickness plate structures is demonstrated in (Fig. 4a), which is a BiOI FESEM image.In comparison to a synthesized structure, it has a longer length-to-width ratio.Arumugam and coworkers employed an alternate solvent in their research.A nano-sheet formation with a square-like structure was discerned when water (H 2 O-BiOI) was used as a solvent 41 .The morphology of BiOI is affected by the synthesis methods, chemicals, and solvents that are utilized.The constructed MOF has a thin, disk-like shape (Fig. 4b).The structure of a MOF can be altered by adjusting the organic-metal ratio.Findings have suggested that MOF structures transform from rectangular to round as organic linkers increase.The uniformity of the nanoplate morphology of NH2-MIL125(Ti) was observed in Zhang and coworkers' study 42 .BiOI-MOF is depicted in (Fig. 4c) as a rod with small particles.The structure of BiOI-MOF was comparable to Du and colleagues' analysis 43 .Furthermore, (Fig. 4d) displays the EDX image of BiOI.The samples show varying proportions of the primary components of each structure.The TEM image, depicted in (Fig. 4e), illustrates the effective dispersion of the NH 2 -MIL125(Ti) composite onto the BiOI surface, resulting in the formation of a core-shell architecture.Additional information regarding the structure of the BiOI, MOF, and BiOI-MOF catalysts is presented in (Figs.S1-S3) to enhance comprehension.

BET analysis
Figure 5 displays the nitrogen adsorption-desorption isotherms for BiOI-MOF.The relationship between pressure and adsorption/desorption rate is significant.The hysteresis is classified as H3 and type IV due to its curved shape.This particular type of hysteresis is present in a non-hard cavity that has been cut into a certain shape.The tensile strength effect has a strong slope and is also known as the H 3 hysteresis repulsion branch.The precursor's BET surface area and pore volume were determined using the N2 adsorption-desorption isotherm and BJH techniques, and were found to be 939.92m 2 /g and 16.17 cm 3 /g, respectively.

UV-vis analysis
The UV-visible spectrum is displayed in (Fig. 6).The boundary line of BiOI, MOF and BiOI-MOF are located at 635, 505 and 685 nm respectively.The analysis reveals that BiOI-MOF has a greater band edge than either BiOI or MOF independently.Since the band gap has been found to be within the visible light spectrum, it can be concluded that the catalyst can be activated by visible light.Moreover, the DRS analysis revealed that the main catalyst has a narrower band gap against BiOI and MOF and uses low energy for activation.When compared to BiOI and MOF, the BiOI-MOF's structure has changed, as evidenced by the alterations made to the boundary line and diffuse reflectance.At 685 nm, the range line has grown.Furthermore, the band gap is now 3.62 eV.These modifications may have an impact on the catalyst's electrical characteristics and enhance its capacity for charge separation and photocatalysis.Comparable findings were reported in our earlier research 21 .
XPS analysis XPS (Fig. 7) was used to evaluate the chemical state and surface composition of BiOI-MOF.The XPS spectrum affirms the components of Bi, I, Ti, O and C elements.Additionally, the purification of BiOI and NH 2 -MIL125(Ti) is verified.Table S1 summarizes the BiOI-MOF components.Jiang and their colleagues obtained similar outcomes 44 .By analyzing the XRD results, which include changes in the spectrum such as peak removal, formation of new peaks, shift in peak positions, and changes in peak intensity, as well as analyzing the morphology of the BiOI-MOF catalyst in comparison to BiOI and NH 2 -MIL125(Ti), conducting EDS elemental mapping analysis to determine the presence of elements on the catalyst surface, analyzing the weight percentage and element ratio in EDS analysis, and confirming the presence of Ti, Bi, N, C, and I elements through XPS analysis, it can be concluded that the heterogeneous connection between BiOI and NH 2 -MIL125(Ti) has been successfully achieved and the BiOI-MOF catalyst has been synthesized correctly.S2).For identifying the data deviation factors in an ANOVA study, the F-value and P-value are trustworthy statistical markers.A significant statistical model with a high F-value and a low p-value (≤ 0.05) was chosen as a result of these indexes.A quadratic model would  S3).
Utilizing ANOVA, the data for tocilizumab degradation (Table S4) exhibited a high level of reliability and a significantly low probability value for the quadratic regression model, indicating its strong capability to effectively describe the patterns within the real data and predicted values.This model proved to be highly accurate and skilled in forecasting responses, as evidenced by the correlation coefficients (R 2 , R 2 adj , and R 2 predict).A strong correlation exists among R2, R2adj, and R2 predict, demonstrating the model's ability to make accurate predictions 45,46 .The F-value for the degradation of tocilizumab has been calculated to be 347.93 and the P-value (0.0001) strongly indicate a successful fit between the experimental and expected response values.An Adequate Precision ratio of greater than 4.0 indicates an acceptable model.The equation for the percentage of tocilizumab removal was expressed in terms of coded factors as follows: The removal of tocilizumab was affected by the studied mediators, as outlined in (Eq.10).The quadratic model showed a CV lower than 10%, confirming the accuracy and repeatability of the experiments.Furthermore, it was established that all interactions between the variables were of significance.Statistical analysis indicated that there was a statistically significant correlation between variables and the removal of tocilizumab.
The influence of factors on the tocilizumab degradation from O 3 -HPCP pH of solution.The efficiency of O 3 -HPCP is notably impacted by the solution's pH.The outcomes of varying pH levels (ranging from 4 to 8) on the efficiency of tocilizumab removal are depicted in Fig. 8.As the pH of the solution increased, there was a significant enhancement in the removal efficiency of tocilizumab, reaching its peak efficacy at slightly acidic pH levels, approximately around 6. The pH of the solution plays a role in several processes, including the hydrolysis of pollutants, the ionization of pollutants, the characteristics of the catalyst surface, the activity of oxidants and reactive species, as well as the degradation pathway.Also, zero-point charge pH (pH zpc ) of catalyst and pKa of tocilizumab have an important role in efficiency degradation of pollutant.The most effective degradation of tocilizumab appears to be when the pH is at the (pH zpc ) of 6.3 for BiOI-MOF.If the pH is below 6.3, the photocatalyst has a positive charge on its surface, but when the pH is above 6.3 it has a negative charge.Due to the pKa of tocilizumab being 6.8, a more acidic pH than that of the zero-point charge encourages the adsorption of tocilizumab molecules on the photocatalyst surface, leading to an enhanced degradation of the photocatalyst in weakly acidic conditions.An elevation in pH levels results in heightened  coulombic repulsion between the negatively charged surface of BiOI-MOF and the OH − species involved in the photocatalytic oxidation process.This, in turn, diminishes the efficiency of degradation.The pH can influence electrostatic interactions between functional groups of the catalyst, such as ionization in this scenario 47 .Ozone breaks down fast into free radicals at higher pH levels, which have a far greater speed and efficiency of breaking down organic materials than ozone molecules 48 .It was noted that the pH zpc value of the photocatalyst measured 6.3, thereby indicating that the surfaces of the photocatalyst possess the ability to act as protonating and nonprotonating agents in lower and higher pHzpc ranges, respectively.Subsequently, upon the reduction of the pH level, minimal adsorption was observed as a result of the electrostatic repulsion between the catalyst, which carried a positive charge, and the tocilizumab molecules that had undergone protonation.Several studies have showed that the decomposition of contaminants typically occurs through direct and indirect oxidation mechanism during an ozonation process.The direct reaction of tocilizumab and ozone is observed at lower pH levels.As the pH of the solution increased, there was an increase in the rate of ozone decomposition and the production of free radicals, accompanied by the generation of free radicals with a high potential for oxidation.These radicals have a greater capability for tocilizumab decomposition.The molecules of tocilizumab can interact indirectly with free radicals in a basic environment, leading to improved removal performance.Asgari et al. investigated the capability of the photocatalytic ozonation process to removal of ceftazide.According to this study, a pH value of 11.0 was the most desirable pH of the solution 49 .Similarly, Jonathan C. Espíndola et al. reported findings of their own 50 .Dose of catalyst.The quantity of the catalyst is a critical parameter that impacts heterogeneous-AOPs that are based on the catalyst.The research conducted in this study investigated various amounts of BiOI-MOF to determine the effectiveness of O 3 -HPCP in removing tocilizumab (Fig. 8).Results demonstrated that the removal efficacy of tocilizumab was notably improved when the catalyst dose increased from 0.25 to 0.5 mg/l.In spite of this, catalyst dosages of 0.46 mg/l did not show any noteworthy differences.A higher level of catalyst dose had an unfavorable effect on O 3 -HPCP.Generally, this effect is caused by particles amassing and clustering together, www.nature.com/scientificreports/leading to a decline of surface active sites.When there is too much catalyst in the solution, UV light can be diffused, which prevents ozone and UV radiation from reaching the catalyst surface.The surface area of the active site for photocatalytic activity can be increased by adding more catalyst.Because of this, the nanoparticles had a higher level of ozone adhesion, leading to the generation of more active radicals due to ozone destruction.This resulted in an increase of tocilizumab removal effectiveness.In addition, oxygen radicals are produced when nanoparticles and ozone are combined in an alkaline environment.Oxygen radicals in water stimulate the formation of • OH radicals, which increases ozonation efficiency 48 .Other studies of photocatalytic ozonation have come to similar conclusions, which are consistent with this study.Lu and their colleagues conducted an investigation of tetracycline hydrochloride decomposition through photocatalytic ozonation.This study used a catalyst of 0.0 to 0.8 g/l of Bi 2 WO 6 .The process had an efficiency of 78% when the dose was 0.5 g/l, however within 120 min this dropped to 65% when it reached 0.8 g/l 51 .Results consistent with Yu et al. 's study were discovered 52 .
Ozone concentration.The most significant economic factor in O 3 -HPCP is the amount of inlet ozone.This factor is strongly connected to energy utilization.The range of ozone gas concentration studied in this study was from 20 to 40 mM/l-min (Fig. 8).According to the findings, the process's efficiency increased somewhat when the ozone concentration was changed from 20 to 30 mMol/l-min.Increased ozone concentrations cause the rate of mass transfer in the reaction medium to increase.As the rate of ozone gas flow increases, the concentration of dissolved ozone in the solution rises.Reactive oxygen species, especially hydroxyl radicals, generate in greater quantities as a result of the synergistic impact.Adsorption of dissolved ozone molecules by photocatalysts is made easy due to the weak hydrogen bonds with their surface hydroxyl groups.Electron capture on the surface of the photocatalyst results in the formation of anions of ozonide radicals.Therefore, the ozonide radicals (O 3 •− ) heighten the level of • OH radicals and the potency of tocilizumab degradation 51 .In contrast, if the air flow coming in is too much, and the rate of moving from gas to liquid is slow, the ability to remove will be decreased.In general, the kind of procedure, kind of reaction reactor, type of pollutant, and specifications of the intermediate chemicals all affect the amount of ozone required for O 3 -HPCP 53 .Previous studies have reported various concentrations of ozone as being optimal.The optimal ozone concentration was reported by Heydari et al. 54 at 11 mg/l, while Yu et al. 55 reported 1.5 mg/l-min.
Reaction time.Another important component influencing heterogeneous AOPs is reaction time.This research explored the effect of reaction time on the removal of tocilizumab in the timeframe of 30 to 60 min (Fig. 8).There was a marked improvement in degradation effectiveness for tocilizumab with increasing reaction time.As previously noted, O 3 -HPCP remove tocilizumab by two distinct oxidation pathways.Ozone molecules, photolysis and free radicals as well as electron-hole pairs created can all contribute to pollutant destruction through indirect and direct oxidation.The reaction time was increased, leading to complete pollutant destruction and mineralization with a decreased number of intermediate compounds.Consequently, the ideal reaction time depends on the kind of pollutant, qualities of the reaction reactor, other operational variables and conditions.Various reaction time have been highlighted in prior investigations.Lu et al. 51 , report 120 min as the optimal time.The optimal value of experiment parameters for tocilizumab degradation by O 3 -HPCP was ultimately determined by us using the Design-Expert software.The ideal conditions for process were pH of the solution 7.0, catalyst dose of 0.46 mg/l, reaction time of 59 min, concentration of 32 mMol/l-min, and initial tocilizumab concentration of 10 mg/l.Here, tocilizumab was degraded 92%.

Synergist effect, recyclability of photocatalyst, COD and TOC test
Results from (Fig. 9a) demonstrate the functionality of single mechanisms, dual mechanisms and O 3 -HPCP in the degradation of tocilizumab under optimal circumstances.According to the findings, sorption (6.9%), ozonation (53%) and photolysis (UV-C = 35%, UV-A = 22, and visible light = 12%) are the three main mechanisms by which tocilizumab degrades.These mechanisms lack sufficient potential.The dual processes of catalytic ozonation (68%), photocatalyst (40%), and photo ozonation (59%) were found to be more successful in degrading tocilizumab than the individual processes.Ultimately, the O 3 -HPCP could remove 92% of the tocilizumab.The findings support the synergistic effect between a variety of mechanisms, leading to a more active degradation of tocilizumab based on ROS s .By following (Eq.8), the SF coefficient yielded a value of 1.22.Photolysis and ozonation were utilized to degrade tocilizumab through direct oxidation.Oxidation with a direct process has limited capacity because of its selectivity.Consequently, the pollutant removal efficiency is evidently inadequate.However, in binary processes and O 3 -HPCP, oxidation is done indirectly through ROS s .These radicals have a capacity of high oxidation for organic pollutants, such as tocilizumab, due to their non-selective properties.When light is directed towards a catalyst in photocatalytic reactions, holes develop in the valence band (VB) and electrons form in the conduction band (CB).Since the catalyst's CB potential is higher than the reaction medium's redox potential for oxygen and oxygen peroxide, electrons are transported to the oxygen and abundantly transformed to oxygen.ROS generation and the use of photogenerated carriers will affect the photocatalytic system 56 .Electrophilic ozone, in comparison to direct ozonation, can be easily used in photocatalytic systems to trap photogenerated electrons.The photogenerated electron of the catalyst is efficiently transferred, causing the electron-hole pairs to be effectively separated when exposed to simulated light irradiation, resulting in a high production of ROS.The ozone utilization ratio can be improved through the use of a catalyst in the photo ozonation process.An increase in ozone during the reaction will create more ROS, which will be helpful regarding the mineralization of organic compounds.The combination of photocatalysis and ozonation produces more ROS than when each process is used separately, making it effective in the removal of organic pollutants 57 .In Lu et al. 51 study, TOC removal in O 3 , O 3 /light and O 3 /light/catalyst were 18, 20 and 78% respectively.As illustrated in (Fig. 9b), the findings of tocilizumab removal, and reduction of COD, and TOC are presented.It has been found out by the results that the COD and TOC reduction rate is lower than that of tocilizumab removal.Tocilizumab, COD, and TOC reduced by 92, 79.8, and 59%, respectively, under ideal circumstances.The current discrepancy demonstrates the generation of organic byproducts and intermediates.The results showed that increasing the reaction time improves COD and TOC reduction.Over 90% of COD and roughly 80% of TOC were decreased in just 100 min.Asgari et al. 48reported 100, 92.3 and 81.1% CIP, COD and TOC removal respectively in 60 min.
The essential characteristics of catalysts for practical applications encompass the capacity to be recycled and utilized again.The (Fig. 10) illustrated the capacity of the photocatalyst to be recycled was investigated over the course of six consecutive cycles in ideal circumstances.The catalyst was taken out of the solution and allowed to dehydrate at 80 °C for 24 h after each cycle.After six consecutive cycles, the removal of tocilizumab demonstrated a 3% reduction.The O 3 -HPCP efficiency somewhat declined, indicating that catalysts could be recycled for a minimum of six cycles.The increasing obstruction of photocatalytic adsorption sites by tocilizumab and co-products, the use of active oxidizing species by intermediates, and the ongoing washing and drying processes might all be contributing factors to the small decline in catalyst activity 49 .Bagheri et al. 58 observed that after eight iterative cycles of catalyst, there was a 92% efficiency in dye degradation.

Quenching tests and ions influence on O 3 -HPCP performance
The results of the quenching test are presented in (Fig. 11a).Tert-butanol, KI, methanol, EDTA, sodium azide, and benzoquinone were chosen as some ROS s scavengers.The results indicated that methanol had the most effect on O 3 -HPCP performance in tocilizumab removal and the lowest effect on performance observed in the sodium azide presence.Because reactive species are responsible for the degradation of organic pollutants in AOPs, it is  essential to understand the principles of AOP s and the process of persistent organic pollution degradation by examining the creation, identification, and reaction mechanism of ROS s in AOP s .There are different methods like electron spin resonance (ESR), transient absorption spectrum, quenching test and HPLC for identification.One indirect way to determine the reactive species in AOP s is to perform the quenching test.The foundation of quenching tests is on the variations in the reactivity and reaction rates between a specific scavenger and a potentially reactive species.The selectivity of the scavenger is a crucial factor in the quenching experiments 59 .ROS s in O 3 -HPCP include OH • , O 2 •− , HO 2 •− , O 3 •− and e − -h + pairs.So, methanol, tert-butanol, KI, benzoquinone, EDTA, and sodium azide were chosen as a α-Hydrogen OH • , OH • , surface OH • , O 2 •− , O 2 1 and O 3 •− , and e − -h + pairs scavengers, respectively.The results revealed that the OH • plays the most important role in pollutant oxidation and the e − -h + pair has the least effect.The α-hydrogen OH • mechanism involves the attack of the highly reactive OH • on the α-carbon, which is situated adjacent to a functional group, in organic compounds.This interaction leads to the degradation of the organic pollutants.Hydroxyl radicals are commonly generated through processes such as the photolysis of hydrogen peroxide under UV light or through direct reaction with ozone.These hydroxyl radicals exhibit strong reactivity and possess potent oxidizing capabilities.Subsequently, the abstraction of the α-hydrogen by the hydroxyl radical generates a carbon-centered radical within the organic pollutant.This radical is also highly reactive and capable of initiating a cascade of reactions.Furthermore, the carbon-centered radical can react with molecular oxygen to yield peroxy radicals (ROO • ).These peroxy radicals can subsequently engage in further reactions with other organic molecules, thereby instigating a chain reaction that degrades the organic pollutant into smaller, less harmful fragments.Ultimately, the chain reaction persists until termination reactions take place.Termination reactions typically involve the recombination of radicals or their reaction with other reactive species, effectively concluding the degradation process 60,61 .In Bashiri et al. 62 , and Li and et al. 63 studies similar results have been reported.
Practical wastewater contains several inorganic ions.Subsequently, it is necessary to investigate how distinct inorganic ions can impact O 3 -HPCP capability to tocilizumab removal., Cl − , and SO 4 2− with 0.1 mM concentration were chosen and the influence on the O 3 -HPCP performance is presented in (Fig. 11b).The reaction of inorganic anions and reactive species is the primary factor of inorganic anions, enabling the formation of a novel ROSs.Since these ROS s have smaller ORP than OH • , the procedure is less efficient.With the existence of SO 4 2 , SO 4 •− generated that has 2.5 eV ORP, and the efficiency is less affected (Eq.11).
In the presence of Cl − ion, the following reactions (Eqs.12 and 13) occur and cause the formation of Cl • (ORP = 2.03 eV), and because it is weaker than OH • , it causes a decrease in the process's efficiency.
In the presence of CO 3 2− ion, the following reaction (Eq.14) occur and cause the formation of CO 3 •− (ORP = 1.7 eV), and because it is weaker than OH • , it causes a decrease in the process's efficiency.(11 In the presence of NO 3 − ion, the following reaction (Eq.15) occur and cause the formation of NO 3 • (ORP = 2.3-2.5 eV), and because it is selective and weaker than OH • , it causes a decrease in the process's efficiency.
In the presence of PO 3 4− ion, the following reaction (Eq.16) occur and cause the formation of PO 4 2•− (ORP = 1.5 eV), and because it is weaker than OH • , it causes a decrease in the process's efficiency.
Analysis of prior studies showed that researchers have examined different anions.Yuan and et al. 64 and Saleh and et al. 65 reported similar reports in owner studies.

Reaction kinetic and electrical energy demand
The first-order model (Eq.7) illustrated the rate of tocilizumab degeneration over O 3 -HPCP in optimal conditions.The degradation of tocilizumab in 10, 15, and 20 mg/l concentrations was showed in (Fig. 12) over 60 min using a linear first-order kinetic model.The first-order model indicates that the degradation of tocilizumab in O 3 -HPCP is accurately reflected by the experimental data (R 2 > 0.98) when the initial concentration is 10 mg/l.Through the evaluation of prior research, it has been found out that first-order kinetics is frequently observed in most AOPs 66,67 .
Energy consumption must be factored into practical applications.The ozone generator and the UV lamp were the source of EEO in this process.EEO in different processes is presented based on Eq. 9 in Table 2.
The results show that in the O 3 -HPCP, based on tocilizumab removal, energy consumption is more appropriate.
Prior studies have demonstrated that the effectiveness of the EEO procedure is contingent upon several factors, including the ozone generator's power, the lamp's power, the reaction time, the reaction chamber's size, and the overall process efficiency 68 .The EEC recorded in Kang et al. research was 55 KWh/m 323 .

catalyst components effect and mechanism of reactions
To compare the photocatalytic effectiveness of the BiOI-MOF component to that of the MOF (NH 2 -MIL125(Ti)) and BiOI components, the study was conducted under optimal conditions.In this section, the results showed (Fig. 13) that when the heteroconjection structure occurs; it improves the photocatalytic properties of the catalyst and increases the efficiency of the process.The surface properties, such as pore volume, active surface area, pollutant specific absorption rate, have been altered in the BiOI/MOF structure in comparison to the pure structures, as well as optical properties such as band gap, consequently leading to an improved efficiency.The ( 14) The O 3 -HPCP mechanism described by (Eq.17     •− .Furthermore, a series of chemical events occur, leading to the creation of various oxidizing radicals, based on the data shown in (Eqs.22-27).This ultimately results in the contaminant degrading, as (Eq.28) illustrates.The combination of BiOI and NH 2 -MIL125(Ti) in the BiOI-MOF catalyst results in a diverse interaction, which enhances the generation of charge under light and reduces the recombination of electron-hole pairs, as compared to the pure BiOI.The mechanism can be attributed to several factors like Heterostructure formation, type-II band alignment, band-edge positions, enhanced surface area and active sites and synergistic effects.These factors collectively promote efficient charge transfer, separation, and utilization, leading to enhanced photoelectrochemical performance.A heterostructure is formed by the combination of BiOI and NH 2 -MIL125(Ti), with the two materials being in close proximity to one other.This heterostructure facilitates efficient charge transfer and separation at the interface.When light is absorbed, electrons in both BiOI and NH 2 -MIL125(Ti) become excited.The heterostructure helps in the effective transport of these excited electrons from BiOI to NH 2 -MIL125(Ti).The energy band alignment between BiOI and NH 2 -MIL125(Ti) exhibits a mostly type-II characteristic.In this band alignment configuration, one material has a valence band maximum (VBM) that is positioned at a higher energy level than the conduction band minimum (CBM) of the other material.The staggered band alignment results in the presence of an inherent electric field at the interface, which facilitates the separation of charges and inhibits the recombination of electrons and holes.The energy levels of the valence and conduction bands in the BiOI-MOF structure undergo modifications in comparison to the pure BiOI.NH 2 -MIL125(Ti) can induce a shift in the energy levels of BiOI, causing the CBM to be positioned higher and the VBM to be positioned lower.This shift in energy levels can generate a beneficial energy gradient that facilitates the efficient separation and movement of charges.NH 2 -MIL125(Ti) is a MOF material characterized by its substantial surface area and numerous active sites.The incorporation of NH 2 -MIL125(Ti) into BiOI enhances the light absorption capacity and introduces supplementary locations for charge separation and transfer.The active sites within the MOF framework serve as trapping or catalytic centers, enabling the separation and use of photogenerated charges.The distinct characteristics and capabilities of each material can synergistically enhance the separation of charges and minimize recombination.NH 2 -MIL125(Ti) may have effective charge transport characteristics, whereas BiOI may have pronounced visible light absorption.The combined impacts of the two materials can greatly enhance the overall photoelectrochemical performance [70][71][72] .

Conclusion
The analysis of BiOI-MOF via XRD, FTIR, FESEM, EDS, EDS elemental mapping, UV-vis, BET and XPS yielded significant findings of catalyst synthesis optimization.According to XRD analysis, the BiOI-MOF displays specific peaks that resemble those seen in the pure BiOI and MOF.However, there is a notable alteration in the locations and intensities of these peaks.The most prominent peaks in the FTIR spectra of the catalyst were observed at wavenumbers of 565.5, 807, 1313, 1382, 1624, and 3464 cm −1 .The peaks can be used to identify amine groups, alkyl halides, -CH 3 signals, N-O nitro compounds, C-H stretching, and C-H bands.The BiOI-MOF was observed in the FESEM as a rod-shaped structure composed of tiny particles.The samples exhibit diverse ratios of the fundamental constituents of each form.The TEM image demonstrates the successful distribution of the NH 2 -MIL125(Ti) composite onto the BiOI surface, leading to the creation of a core-shell structure.The hysteresis is categorized as H 3 and type IV, according to the BET study.The measured values for the surface area and pore volume were 939.92 m 2 /g and 16.17 cm 3 /g, respectively.The relative boundary wavelengths for BiOI, MOF, and BiOI-MOF are 635, 505, and 685nm, respectively.Moreover, the band gap has decreased to 3.62 eV.These alterations can potentially affect the electrical properties of the catalyst and improve its ability to separate charges and facilitate photocatalysis.The XPS spectrum confirms the presence of the elements Bi, I, Ti, O, and C. Furthermore, the validation of the purification process for BiOI and NH 2 -MIL125(Ti) is confirmed.The F-value obtained from the ANOVA analysis for the degradation of tocilizumab is 347.93.The corresponding P-value (0.0001) indicates a highly significant match between the experimental and anticipated response values.The optimal parameters for the process were a solution pH of 7.0, a catalyst dose of 0.46 mg/l, a reaction time of 59 min, a concentration of 32 mMol/l-min, and an initial tocilizumab concentration of 10 mg/l.Here, the degradation of tocilizumab reached 92%.The primary degradation mechanisms of tocilizumab include sorption (6.9%), ozonation (53%), and photolysis (UV-C = 35%, UV-A = 22%, and visible light = 12%).These mechanisms are deficient in their potential.The combined methods of catalytic ozonation (68%), photocatalyst (40%), and photo ozonation (59%) shown more efficacy in degrading tocilizumab compared to the separate processes.COD ( , and e − -h + pairs scavengers, respectively.The results indicated that methanol had the most effect on O 3 -HPCP performance in tocilizumab removal and the lowest effect on performance observed in the sodium azide presence.Furthermore, the results revealed that the OH • plays the most important role in pollutant oxidation and the e − -h + pair has the least effect.SO 4 2− had the lowest effect on the efficiency of the process, and NO 3 − had most effect in anions, the process's efficiency was inhibited by organic scavengers.The rate of reaction follows a firstorder equation (R 2 = 0.98).EEO under optimum condition 161.8 KWh/m 3 -order calculated.The combination of BiOI and NH 2 -MIL125(Ti) in the BiOI-MOF catalyst results in a diverse interaction, which enhances the generation of charge under light and reduces the recombination of electron-hole pairs, as compared to the pure BiOI.The mechanism can be attributed to several factors like Heterostructure formation, type-II band alignment, band-edge positions, enhanced surface area and active sites and synergistic effects.Lastly, a comparison between the current study and earlier research is provided in Table 3.
Table 3. comparison between the current study and earlier research based on O 3 -HPCP.

Figure 8 .
Figure 8. Investigation of the variables' influence on the removal of tocilizumab in the O 3 -HPCP method.

Table 1 .
The range of Factors on Performance of process.

Electric energy per order of pollutant removal P Electric
24) H 2 O 2 → OH − 2 + H + Free radicals + Pollutant → CO 2 + H 2 O + non -toxic inorganic compounds and TOC decreasing under optimum condition was 79.8, and 59% respectively, that lower than tocilizumab removal.The catalyst could be used for six consecutive operations with acceptable results and a 3% reduction in efficiency.ROS s in O 3 -HPCP include OH • , O 2 •− , HO 2 •− , O 3 •− and e − -h + pairs.So, methanol, tert-butanol, KI, benzoquinone, EDTA, and sodium azide were chosen as a α-Hydrogen OH • , OH • , surface OH • , O 2